Research investigated key issues in uterine fibroid treatments

Ronit Machtinger, MD has completed a FUS Foundation-funded, two-year, part-time fellowship at the Brigham & Women’s Hospital (BMH) in Boston, MA, USA. Her fellowship mentors were Clare Tempany, MD and Fiona Fennessy, MD.

An Israeli gynecologist, Machtinger will return to Sheba Medical Center next summer, where she will resume her gynecology practice and continue her work in focused ultrasound. In the meantime, she is completing a research fellowship in reproductive endocrinology and infertility at BWH and is writing a book chapter with Fennessy about focused ultrasound treatment of uterine fibroids.

During her fellowship, Machtinger worked on two key research projects. The first investigated how to successfully treat uterine fibroid patients who have scar tissue from previous pelvic surgeries such as caesarean sections or myomectomies. “The focused ultrasound beam cannot pass safely through scar tissue. Rather, it can defocus and lead to local build-up of skin heat,” she explains.  With her BMH colleagues, she demonstrated that careful pre-treatment planning enables successful treatment of patients with pelvic scar tissue. Their case report was published this year in ISRN Obstetrics and Gynecology.

In the second project, Machtinger investigated whether focused ultrasound is a viable treatment option for African American women, a group in which uterine fibroids are most prevalent and severe. This group also has the highest rate of hysterectomies and complications. Analyzing data from two multi-center clinical trials, Machtinger and her colleagues found that, when appropriately selected for focused ultrasound treatment, African American women had the same overall clinical outcomes as other women.

As part of this second project, Machtinger studied the differences in screening failure rates between African American and other women.  “We showed that African American women were more likely to be screen failures than non-African American women,” she notes. “African Americans were significantly more likely to fail screening due to MRI findings which could interfere with safe delivery of treatment while non-African American women failed screening due to inadequate fibroid-associated symptoms compared to the African American population.”

Machtinger presented the results of the “screen failures” investigation in October 2010 at the 2^nd International Symposium on MR-guided Focused Ultrasound, where she was also honored as a Young Investigator Award recipient. Publication of the project’s complete findings is pending.

Related links:

FUS Foundation fellowship profile for Ronit Machtinger

Final Fellowship report –submitted by Ronit Machtinger in November 2011

Analyzing Screen Failures Prior to MRgFUS for Uterine Fibroids - Ronit Machtinger’s presentation at the 2^nd International Symposium on MR-guided Focused Ultrasound presentation (October 2010)

Publications:

Machtinger R, Tempany CM, Kanan Roddy A, Fennessy FM. Successful MRI-Guided Focused Ultrasound Uterine Fibroid Treatment Despite an Ostomy and Significant Abdominal Wall Scarring. ISRN Obstet Gynecol. 2011; 962621

Machtinger R., Fennessy F.M., Hourvitz M. Book Title: “Image-guided Cancer Therapy: A Multiple-disciplinary Approach” Chapter title: High Focused Ultrasound Treatment for Bone Metastases Chapter no. 47. Editors: William N. McMullen, Dr. Yuman Fong, Dr. Damian Dupuy, Dr. Chul S. Ha and Dr. Jordan Berlin with Associate Editors Dr. Ronnie Poon, Dr. David Lu and Dr. Ricardo Lencioni. Publishers: Springer in press.

Audio/slide presentations by W. Jeffrey Elias, MD and his clinical team at the University of Virginia are now available for viewing on the FUS Foundation website. These talks provide a wealth of background information and were given at a special event organized in September 2011 by the Essential Tremor Support Group in Charlottesville, Virginia. Presentations are listed in the order in which they were given at the event.

Clinical Trial Background - Johanna Loomba, CCRC, Research Coordinator

MR-guided Focused Ultrasound Thalamotomy for Medication- Refractory Essential Tremor - W. Jeffrey Elias, MD, Principal Investigator

Focused Ultrasound Clinical Trial Assessments - Diane S. Huss, PT, DPT, NCS, Board Certified Neurologic Physical Therapist

Personal Experience of a Focused Ultrasound Treatment Patient - John Watterson

By Thomas Gentile, President and CEO of GE Healthcare

The following article is reprinted with permission from GE Healthcare.

When I was in India a few months ago, I first came across an exciting technology called Magnetic Resonance Guided Focused Ultrasound (MRgFUS).  A doctor there was doing investigational research with it to evaluate its use in ablations of tumors.

Using MR scans to pinpoint a target in the body such as a tumor or a uterine fibroid, a doctor can direct a series of high intensity ultrasound beams (as many as 208) on the target to heat the tissue and kill the cells.  It works kind of like a magnifying glass directing a beam of sunlight to a point which then becomes very hot.

One of the leading companies which makes the equipment to perform this technique is called InSightec, a company based in Israel.  The CEO is Kobi Vortman.  GE owns minor equity in InSightec, and Kobi and I had previously met at a conference and have had several phone conversations over the last several weeks.  To help me learn more about MRgFUS, Kobi invited me to visit the University of Virginia to meet some of the doctors who have been doing research with the equipment and to see a demonstration.

Jim Davis, our MR business leader, and Curt Brueske, our Chief Counsel, joined me on the trip.  Jim serves on the Board of Directors for InSightec.  Here are Jim and Curt with Kobi outside the facility which houses a GE 750 3T MR scanner equipped with InSightec’s Exablate technology:

Using a standard MR scanner, the InSightec equipment to conduct the focused ultrasound therapy includes a special customized table where the patient lies.  For body scans, the ultrasound transponder is built into the table.  The University of Virginia also has a separate configuration for its research on potential therapies involving the head.

Here is a picture of the body unit:

The console in front is a standard MR workstation.  The one on the left (which my terrible picture-taking cut in half) is the InSightec console which controls the ultrasound beam.

I took this picture just before we scanned a phantom, and had the chance to program the device to ablate a target within the phantom.  Everything is done by remote control, and the procedure is completely non-invasive.  Each burst of the ultrasound is called a sonication.  A typical procedure might include between 60 and 90 sonications and take from three to four hours.

MR focused ultrasound has many potential uses, and researchers around the world are actively evaluating different indications.  In the US, MRgFUS has FDA approval to be used to ablate uterine fibroids, which are non-malignant tumors in the uterus, in women who have completed child bearing.

For an outstanding description of uterine fibroids and their treatment, please refer to the article by our Chief Medical Officer, Jeff Hersh, from two weeks ago:

http://www.metrowestdailynews.com/lifestyle/columnists/x1876835356/Whats-Up-Doc-Different-treatment-options-for-uterine-fibroids#ixzz1cBE2wvIT

As Jeff describes in his article, there are several ways to treat uterine fibroids.  An invasive technique is a full hysterectomy or removal of the uterus.  A minimally invasive technique is a procedure called a uterine artery embolization, which uses a catheter to cut off the supply of blood to the fibroid.

MR guided focused ultrasound is a non-invasive approach.  I had the chance to speak to Dr. Alan Matsumoto, the Chairman of the University of Virginia Radiology department who is himself an Interventional Radiologist who has performed around 20 MRgFUS on uterine fibroids.  He was very excited about the procedure and we talked for almost an hour about his experiences using it and how he sees it developing in the future.

While we were at the University of Virginia, Jim, Curt and I also had the chance to observe an actual procedure that was part of a research project.  The results were very encouraging and we expect to see some papers in the future on this application of the technology.  I would write more, but I do not want to steal the thunder from the doctors at the University of Virginia.

In general, non-invasive interventional procedures like MR guided focused ultrasound are growing rapidly and have the opportunity to reshape healthcare in the future.

Start-up French device maker, Theraclion, continues to break new clinical ground with its TH-One ultrasonic ablation system. Last month, the company announced early success in the noninvasive treatment of patients with breast fibroadenomas, which are benign tumors that affect about one in ten women and are especially problematic for those under 30 years old. 

Theraclion reported that the first two clinical trial patients at Sofia University Medical Center in Sofia, Bulgaria had significant reduction in tumor volume. Six months after treatment, the patient’s fibroadenomas shrunk in volume by 64 and 62 percent, respectively, and had become softer on palpation. The trial is expected to treat as many as 20 patients before concluding.

David Del Bourgo, MBA

The company has launched a second breast fibroadenoma study in Paris and in Lille. Set to enroll 20 patients over a 6‐month period, the feasibility study will treat women who are scheduled for a surgical resection. Patients will receive focused ultrasound treatment before undergoing surgery. The study will measure high intensity focused ultrasound-induced tissue necrosis assessed by histology of the excised gland two months after treatment.

According to Theraclion, fibroadenoma treatments are performed in a single session under sedation and on an outpatient basis. They take about 30 to 40 minutes, depending on the size of the fibroadenoma.

The TH-One previously achieved successful results in clinical trials for thyroid nodules and primary and secondary hyperparathyroidism. The system, which was originally designed to meet the high precision requirements for administering focused ultrasound to the neck, received CE-marking in 2007 for thyroid and parathyroid applications.

Theralcion’s Vice President of Marketing and Sales, David Del Bourgo, MBA, reports that a prestigious oncology center in France, the Institut Gustave Roussy, is interested in launching clinical trials to explore a fourth indication for the TH-One: metastatic bone tumors.

Del Bourgo says that, in late 2012, Theralicion will begin commercializing the TH-One as a single platform solution for multiple indications to enable hospitals and clinics to justify its acquisition cost.

Project on elastography-guided ultrasound therapy

In addition to exploring new applications of the TH-One, Theraclion is engaged in R&D efforts to improve the system’s guidance technology. In 2009, the company received a €8.5 million grant from the French state innovation agency, OSEO, to embark upon a strategic industrial innovation project on elastography-guided ultrasound therapy. The company‘s partner on the project is SuperSonic Imagine, a leader in ultrasound imaging.

When the grant was announced, Jacques Souquet, PhD, CEO of SuperSonic Imagine, said,  “The added value contributed by SuperSonic Imagine and its Aixplorer product relates to how Theraclion’s therapeutic system is guided. Very high-resolution ultrasound imaging and the superposition of ShearWave elastographic information (a measure of tissue hardness) enable us to determine the site, extent and degree of necrosis created by the Theraclion device."

SuperSonic Imagine’s tissue elasticity imaging concept is quantitative, has reproducible results and works in real time.

“We believe that ultrasound-guidance is becoming a complementary tool to FUSgMR and that elastography is a smart solution to monitor and control tissue necrosis,” observes Del Bourgo.

Theraclion now in fundraising mode

Spun-off in 2004 from French medical equipment company EDAP-Technomed, Theraclion, is based in the Paris area, has ten employees and is supported by an international scientific and medical committee composed of surgeons, interventional radiologists, endocrinologists and nephrologists. 

The company’s main shareholder is Truffle Capital, a leading venture capital firm in Europe. Theraclion has also received significant funding from the French Government through its Innovation and Development Fund, OSEO. 

According to Del Bourgo, Theraclion is now in the midst of major fund-raising. Funding will be used to support planned clinical trials and commercialization initiatives.

TH-One ultrasonic ablation system

The TH-One is a compact, mobile machine with unique technology that combines ultrasound imaging and HIFU treatment systems. It uses diagnostic ultrasound to identify the target and then high-intensity ultrasound to heat and rapidly destroy diseased tissue - thus enabling patients to avoid burdensome drug treatment and the risks of surgery.

“Because it’s mobile and compact, the TH-One can be rolled into the treatment suite and then put back away,” says Del Bourgo.

The system consists of an ultrasound generator, a power amplifier, a computer and a Vizualisation and Treatment Unit (VTU). Currently guided by real-time echography, it offers an excellent image quality, millimeter‐scale shot accuracy and an integrated cooling device for patient safety and comfort.

A unique feature of the TH-One system is the one-use, disposable treatment pack. This treatment pack enables a high-quality, continuous coupling of the ultrasound beam and cooling of the patient skin to ensure safety.

“We believe we have the scalpel of the future. It’s a very elegant, cost-effective, and novel tool for clinicians and patients,” Del Bourgo says. “We don’t want to interrupt existing patient flow and ownership. Rather, we want to provide an additional tool to surgeons and interventional radiologists.

Sources of additional information:

Website: http://www.theraclion.com/

Facebook Page: http://www.facebook.com/pages/Theraclion/303792825050

Vice President of Marketing and Sales, David Del Bourgo: This e-mail address is being protected from spambots. You need JavaScript enabled to view it.

Related links:

TH-One patient treatments: http://www.youtube.com/watch?v=xrYwFI-1Lpo

Company overview: http://www.youtube.com/watch?v=KQXDma_hHTM  As